L-asparaginase activity in plasma and other biological fluids

✍ Scribed by Morton K. Schwartz; Edward D. Lash; Herbert F. Oettgen; Frank A. Tomao

• Publisher: John Wiley and Sons
• Year: 1970
• Tongue: English
• Weight: 962 KB
• Volume: 25
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/1097-0142(197002)25:2<244::aid-cncr2820250203>3.0.co;2-v

✦ Synopsis

An automated method has been developed for the assay of L-asparaginase activity in plasma and other biological fluids. By means of this method, C asparaginase activity has been determined in plasma, cerebrospinal fluid, and urine in patients receiving E. coli L-asparaginase (EC-2) therapy. T h e height of the plasma activity was related to the dosage. In some patients, the plasma enzyme activity fell despite continued administration of L-asparaginase. The disappearance of the E. coli L-asparaginase from the plasma was related to the commercial source of the enzyme. From one source the half-life in adults was 11.2 k 2.7 hours and from another, 22.6 2 4.7 hours. Intramuscular administration of enzyme resulted in plasma levels that were about half those observed following intravenous administration of enzyme. Following intravenous administration of L-asparaginase at doses up to 5000 IU/kg/day, no activity was found in urine. At the highest dosage levels, small amounts of activity were observed in cerebrospinal fluid. When enzyme was injected directly into the cerebrospinal fluid, there was a rapid transfer of enzyme to the plasma, and the activity in the spinal fluid was reduced to negligible amounts within 24 hours.

-ASPARAGINASE (L-ASPARAGINE AMINOHYDRO-L lase EC 3.5.1.1), the enzyme which catalyzes the hydrolysis of asparagine to form aspartic acid and ammonia, is present in many animal tissues, bacteria, and plank20 It is found in the serum of guinea pigs and other rodents, but not in that of man.13 One of the isozymes of L-asparaginase (EC-2) purified from Escherichia coli, the enzyme from guinea pig serum and, to a lesser extent, that purified from chicken liver cause the regression of certain lymphomatous tumors of mice, rats, and dogs.3, 4. 17

Clinical trials with purified E . coli asparaginase (EC-2) have indicated a sensitivity of lymphoblastic leukemia in man to this